What is the pathophysiology of refeeding syndrome?

From the Guidelines

Refeeding syndrome is a potentially fatal metabolic complication that occurs when nutritional support is reintroduced too rapidly in malnourished patients, characterized by dramatic shifts in electrolytes and fluid balance triggered by the sudden transition from a catabolic to an anabolic state. The pathophysiology of refeeding syndrome involves the body's adaptation to undernutrition by down-regulating membrane pumping to conserve energy, leading to leakage of intracellular potassium, magnesium, calcium, and phosphate, with subsequent whole body depletion 1. When refeeding begins, carbohydrate intake stimulates insulin release, which drives glucose, phosphate, potassium, and magnesium into cells for glycolysis and protein synthesis, causing severe hypophosphatemia, hypokalemia, and hypomagnesemia in the serum 1.

Key Factors Contributing to Refeeding Syndrome

• Prolonged starvation leading to decreased insulin secretion and increased glucagon, resulting in breakdown of fat and protein for energy while conserving intracellular minerals like phosphate, potassium, and magnesium
• Sudden transition from a catabolic to an anabolic state, triggering insulin release and driving glucose, phosphate, potassium, and magnesium into cells
• Thiamine deficiency, which can be exacerbated by increased carbohydrate metabolism, risking Wernicke's encephalopathy
• Abnormal sodium and fluid balance, changes in glucose, protein, and fat metabolism, and hypokalaemia and hypomagnesaemia 1

Prevention and Management of Refeeding Syndrome

• Nutrition should be reintroduced gradually, starting at 5-10 kcal/kg/day, with close monitoring of electrolytes and fluid balance 1
• Electrolytes, including potassium, phosphate, and magnesium, should be monitored and replaced proactively
• Thiamine supplementation (100-300 mg daily) should be given before starting nutritional support in high-risk patients
• Volume of circulation, fluid balance, heart rate and rhythm, as well as clinical status should be monitored closely 1

From the Research

Pathophysiology of Refeeding Syndrome

The pathophysiology of refeeding syndrome is characterized by electrolyte imbalances that occur in malnourished and abruptly refed patients 2. The typical features of refeeding syndrome include:

• Hypophosphatemia
• Hypokalemia
• Hypomagnesemia
• Thiamine deficiency

Metabolic Disturbances

Refeeding syndrome describes a constellation of metabolic disturbances that occur as a result of reinstitution of nutrition to patients who are starved or severely malnourished 3. These disturbances can lead to:

• Fluid and electrolyte disorders
• Neurologic complications
• Pulmonary complications
• Cardiac complications
• Neuromuscular complications
• Hematologic complications

Clinical Characteristics

The clinical characteristics of refeeding syndrome include:

• Hypophosphataemia as the hallmark feature 4
• Other biochemical abnormalities such as hypokalaemia, hypomagnesaemia, thiamine deficiency, and disorder of sodium and fluid balance 4
• Abnormal glucose metabolism and certain vitamin deficiencies 5
• Abnormalities affecting multiple organ systems, including neurological, pulmonary, cardiac, neuromuscular, and haematological functions 5

Prevention and Treatment

The prevention and treatment of refeeding syndrome involve:

• Identifying patients at risk 3, 5
• Instituting nutrition support cautiously 3
• Correcting and supplementing electrolyte and vitamin deficiencies to avoid refeeding syndrome 3
• Reintroducing nutrition cautiously and correcting electrolyte and vitamin deficiencies properly 5